College of Medicine and Public Health & Centre for Neuroscience, Flinders University, Discipline of Human Physiology, Adelaide, SA, Australia.
College of Science and Engineering, Flinders University, Adelaide, SA, Australia.
J Physiol. 2019 Oct;597(20):5125-5140. doi: 10.1113/JP278284. Epub 2019 Oct 1.
Enteric neural circuits enable isolated preparations of guinea-pig distal colon to propel solid and fluid contents by a self-sustaining neuromechanical loop process. In addition there are at least three neural mechanisms which are not directly involved in propulsion: cyclic motor complexes, transient neural events and distal colon migrating motor complexes. In excised guinea-pig colon we simultaneously recorded high resolution manometry, video-imaging of colonic wall movements and electrophysiological recordings from smooth muscle, which enabled us to identify mechanisms that underlie the propulsion of colonic content. The results show that the intermittent propulsion during emptying of the multiple natural faecal pellets is due to the intermittent activation of cyclic motor complexes and this is facilitated by transient neural events. Loss or dysfunction of these activities is likely to underlie disordered gastrointestinal transit.
It is well known that there are different patterns of electrical activity in smooth muscle cells along different regions of the gastrointestinal tract. These different patterns can be generated by myogenic and/or neurogenic mechanisms. However, what patterns of electrical activity underlie the propulsion of natural faecal content remains unknown, particularly along the large intestine, where large quantities of water are reabsorbed and semi-solid faeces form. In this study, we developed a novel approach which enables for the first time the simultaneous recording of high resolution intraluminal manometry, electrophysiology from the smooth muscle, and spatio-temporal video imaging of colonic wall movements. Using this approach we were able to reveal the nature of enteric neuromuscular transmission and patterns of motor activity responsible for the movement of content. Three distinct neurogenic patterns of electrical activity were recorded even in the absence of propulsive movement. These were the cyclic motor complexes (CMCs), the transient neural events (TNEs) and the slowly propagating distal colonic migrating motor complexes (DCMMCs). We present evidence that the initiation of pellet propulsion is due to a cyclic motor complex (CMC) occurring oral to the pellet. Furthermore, we discovered that the intermittent propulsion of natural faecal pellets is generated by intermittent activation of CMCs; and this propulsion is facilitated by hexamethonium-sensitive TNEs. However, TNEs were not required for propulsion. The findings reveal the patterns of electrical activity that underlie propulsion of natural colonic content and demonstrate that propulsion is generated by a complex interplay between distinct enteric neural circuits.
肠神经回路使分离的豚鼠远端结肠标本能够通过自维持的神经机械环路过程推进固体和液体内容物。此外，还有至少三种不直接参与推进的神经机制：周期性运动复合物、短暂的神经事件和远端结肠移行性运动复合物。在离体的豚鼠结肠中，我们同时记录高分辨率测压、结肠壁运动的视频成像和平滑肌的电生理记录，这使我们能够确定推动结肠内容物的机制。结果表明，排空多个自然粪便颗粒时的间歇性推进是由于周期性运动复合物的间歇性激活，而短暂的神经事件则促进了这种激活。这些活动的丧失或功能障碍可能是胃肠道传输紊乱的基础。
众所周知，胃肠道不同区域的平滑肌细胞存在不同的电活动模式。这些不同的模式可以通过肌源性和/或神经源性机制产生。然而，推动自然粪便内容物的电活动模式仍然未知，特别是在大肠中，大量的水被重吸收，半固体粪便形成。在这项研究中，我们开发了一种新方法，使我们能够首次同时记录高分辨率腔内测压、平滑肌的电生理和结肠壁运动的时空视频成像。使用这种方法，我们能够揭示负责内容物运动的肠神经肌肉传递和运动活动的性质。即使在没有推进运动的情况下，也记录到三种不同的神经源性电活动模式。这些是周期性运动复合物（CMCs）、短暂的神经事件（TNEs）和缓慢传播的远端结肠移行性运动复合物（DCMMCs）。我们有证据表明，颗粒推进的启动是由于颗粒口侧的周期性运动复合物（CMC）的发生。此外，我们发现，自然粪便颗粒的间歇性推进是由 CMC 的间歇性激活产生的；这种推进是由六烃季铵敏感的 TNEs 促进的。然而，TNEs 并不是推进所必需的。这些发现揭示了推动自然结肠内容物的电活动模式，并表明推进是由不同的肠神经回路的复杂相互作用产生的。
